Selective Adaptation in Speech: Measuring the Effects of Visual and Lexical Contexts

Published Aug 1, 2021Speech selective adaptation is a phenomenon in which repeated presentation of a speech stimulus alters subsequent phonetic categorization. Prior work has reported that lexical, but not multisensory, context influences selective adaptation. This dissociation suggests that lexical and multisensory contexts influence speech perception through separate and independent processes (see Samuel & Lieblich, 2014). However, this dissociation is based on results reported by different studies using different stimuli. This leaves open the possibility that the divergent effects of multisensory and lexical contexts on selective adaptation may be the result of idiosyncratic differences in the stimuli rather than separate perceptual processes. The present investigation used a single stimulus set to compare the selective adaptation produced by lexical and multisensory contexts. In contrast to the apparent dissociation in the literature, we find that multisensory information can in fact support selective adaptation.Support for this project was provided by NSF Grant 1632530 to Lawrence D. Rosenblum as well as the Spanish Ministry of Science and Innovation, Grant PSI2017-82563-P, awarded to Arthur G. Samuel and was partially supported by the Basque Government through the BERC 2018-2021 program, and by the Spanish State Research Agency through BCBL Severo Ochoa excellence accreditation SEV-2015-0490 awarded to Arthur G. Samuel

Targeting EZH2 Reprograms Intratumoral Regulatory T Cells to Enhance Cancer Immunity.

Regulatory T cells (Tregs) are critical for maintaining immune homeostasis, but their presence in tumor tissues impairs anti-tumor immunity and portends poor prognoses in cancer patients. Here, we reveal a mechanism to selectively target and reprogram the function of tumor-infiltrating Tregs (TI-Tregs) by exploiting their dependency on the histone H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) in tumors. Disruption of EZH2 activity in Tregs, either pharmacologically or genetically, drove the acquisition of pro-inflammatory functions in TI-Tregs, remodeling the tumor microenvironment and enhancing the recruitment and function of CD8+ and CD4+ effector T cells that eliminate tumors. Moreover, abolishing EZH2 function in Tregs was mechanistically distinct from, more potent than, and less toxic than a generalized Treg depletion approach. This study reveals a strategy to target Tregs in cancer that mitigates autoimmunity by reprogramming their function in tumors to enhance anti-cancer immunity

Protein crystal growth results from the United States Microgravity Laboratory-1 mission

Protein crystal growth experiments have been performed by this laboratory on 18 Space Shuttle missions since April, 1985. In addition, a number of microgravity experiments also have been performed and reported by other investigators. These Space Shuttle missions have been used to grow crystals of a variety of proteins using vapor diffusion, liquid diffusion, and temperature-induced crystallization techniques. The United States Microgravity Laboratory - 1 mission (USML-1, June 25 - July 9, 1992) was a Spacelab mission dedicated to experiments involved in materials processing. New protein crystal growth hardware was developed to allow in orbit examination of initial crystal growth results, the knowledge from which was used on subsequent days to prepare new crystal growth experiments. In addition, new seeding hardware and techniques were tested as well as techniques that would prepare crystals for analysis by x-ray diffraction, a capability projected for the planned Space Station. Hardware that was specifically developed for the USML-1 mission will be discussed along with the experimental results from this mission

Phase II Trial of IL-12 Plasmid Transfection and PD-1 Blockade in Immunologically Quiescent Melanoma.

PurposeTumors with low frequencies of checkpoint positive tumor-infiltrating lymphocytes (cpTIL) have a low likelihood of response to PD-1 blockade. We conducted a prospective multicenter phase II trial of intratumoral plasmid IL-12 (tavokinogene telseplasmid; "tavo") electroporation combined with pembrolizumab in patients with advanced melanoma with low frequencies of checkpoint positive cytotoxic lymphocytes (cpCTL).Patients and methodsTavo was administered intratumorally days 1, 5, and 8 every 6 weeks while pembrolizumab (200 mg, i.v.) was administered every 3 weeks. The primary endpoint was objective response rate (ORR) by RECIST, secondary endpoints included duration of response, overall survival and progression-free survival. Toxicity was evaluated by the CTCAE v4. Extensive correlative analysis was done.ResultsThe combination of tavo and pembrolizumab was well tolerated with adverse events similar to those previously reported with pembrolizumab alone. Patients had a 41% ORR (n = 22, RECIST 1.1) with 36% complete responses. Correlative analysis showed that the combination enhanced immune infiltration and sustained the IL-12/IFNγ feed-forward cycle, driving intratumoral cross-presenting dendritic cell subsets with increased TILs, emerging T cell receptor clones and, ultimately, systemic cellular immune responses.ConclusionsThe combination of tavo and pembrolizumab was associated with a higher than expected response rate in this poorly immunogenic population. No new or unexpected toxicities were observed. Correlative analysis showed T cell infiltration with enhanced immunity paralleling the clinical activity in low cpCTL tumors

Inflammatory chemokine receptors regulate CD8+ T cell contraction and memory generation following infection

CD8+ T cells lacking CXCR3 and CCR5 expression have impaired contraction and generate an increased number of memory cells after virus infection

Genomic analysis of atypical fibroxanthoma

Atypical fibroxanthoma (AFX), is a rare type of skin cancer affecting older individuals with sun damaged skin. Since there is limited genomic information about AFX, our study seeks to improve the understanding of AFX through whole-exome and RNA sequencing of 8 matched tumor-normal samples. AFX is a highly mutated malignancy with recurrent mutations in a number of genes, including COL11A1, ERBB4, CSMD3, and FAT1. The majority of mutations identified were UV signature (C>T in dipyrimidines). We observed deletion of chromosomal segments on chr9p and chr13q, including tumor suppressor genes such as KANK1 and CDKN2A, but no gene fusions were found. Gene expression profiling revealed several biological pathways that are upregulated in AFX, including tumor associated macrophage response, GPCR signaling, and epithelial to mesenchymal transition (EMT). To further investigate the presence of EMT in AFX, we conducted a gene expression meta-analysis that incorporated RNA-seq data from dermal fibroblasts and keratinocytes. Ours is the first study to employ high throughput sequencing for molecular profiling of AFX. These data provide valuable insights to inform models of carcinogenesis and additional research towards tumor-directed therapy

The Benefit of Bimodal Training in Voice Learning

It is known that talkers can be recognized by listening to their specific vocal qualities—breathiness and fundamental frequencies. However, talker identification can also occur by focusing on the talkers’ unique articulatory style, which is known to be available auditorily and visually and can be shared across modalities. Evidence shows that voices heard while seeing talkers’ faces are later recognized better on their own compared to the voices heard alone. The present study investigated whether the facilitation of voice learning through facial cues relies on talker-specific articulatory or nonarticulatory facial information. Participants were initially trained to learn the voices of ten talkers presented either on their own or together with (a) an articulating face, (b) a static face, or (c) an isolated articulating mouth. Participants were then tested on recognizing the voices on their own regardless of their training modality. Consistent with previous research, voices learned with articulating faces were recognized better on their own compared to voices learned alone. However, isolated articulating mouths did not provide an advantage in learning the voices. The results demonstrated that learning voices while seeing faces resulted in better voice learning compared to the voices learned alone

Visibility of speech articulation enhances auditory phonetic convergence

Talkers automatically imitate aspects of perceived speech, a phenomenon known as phonetic convergence. Talkers have previously been found to converge to auditory and visual speech information. Furthermore, talkers converge more to the speech of a conversational partner who is seen and heard, relative to one who is just heard (Dias & Rosenblum Perception, 40, 1457-1466, 2011). A question raised by this finding is what visual information facilitates the enhancement effect. In the following experiments, we investigated the possible contributions of visible speech articulation to visual enhancement of phonetic convergence within the noninteractive context of a shadowing task. In Experiment 1, we examined the influence of the visibility of a talker on phonetic convergence when shadowing auditory speech either in the clear or in low-level auditory noise. The results suggest that visual speech can compensate for convergence that is reduced by auditory noise masking. Experiment 2 further established the visibility of articulatory mouth movements as being important to the visual enhancement of phonetic convergence. Furthermore, the word frequency and phonological neighborhood density characteristics of the words shadowed were found to significantly predict phonetic convergence in both experiments. Consistent with previous findings (e.g., Goldinger Psychological Review, 105, 251-279, 1998), phonetic convergence was greater when shadowing low-frequency words. Convergence was also found to be greater for low-density words, contrasting with previous predictions of the effect of phonological neighborhood density on auditory phonetic convergence (e.g., Pardo, Jordan, Mallari, Scanlon, & Lewandowski Journal of Memory and Language, 69, 183-195, 2013). Implications of the results for a gestural account of phonetic convergence are discussed